The project's focus is on describing the characteristic losses in muscle strength, muscle mass, and physical functioning that occur with aging by examining the entire adult lifespan and the impact on function and longevity. We previously demonstrated that declining muscle strength and rate of change of muscle strength are independent contributors to mortality in men when considering age, physical activity and muscle mass. Further, strength is directly related to walking speed, which is a risk for functional disability in the elderly. We have also shown that muscle power and movement speed are additional independent sarcopenic factors that contribute to longevity. In the past year, we participated in an international collaborative study which conducted a quantitative systematic review and meta-analysis of published and unpublished data, examining the associations between physical capability (grip strength, walking speed, chair rising and standing balance times) and mortality in community-dwelling populations. We found associations between poorer performance on physical capability and increased mortality. Muscle strength and the use of that strength for physical functioning are important contributors to health and longevity. A key contributor for the maintenance and utilization of muscle is the nervous system. Previously, we have shown that peripheral nerve function has an impact on muscle strength and power independent of body size and activity levels. To further examine the effect of age on peripheral nervous function, we examined motor unit characteristics (size and firing rate), using surface and intramuscular electromyography. Surface-represented motor unit size and firing rate were collected from the vastus medialis during knee extension at 10%, 20%, 30%, and 50% of maximum isometric voluntary contraction. Both firing rate and motor unit size per Newton force generated began to increase in the 6th decade of life in this large muscle. The observation suggests that force generation requires greater nervous system activity to obtain a given force level as we age as an adjustment for the decrease in strength, decline in movement speed and response times observed in aging individuals. Alterations in both the peripheral and central nervous systems seem to be major contributors to the sarcopenic process. In related work we have demonstrated that declines with age in vibrotactile sensitivity in the feet are directly associated with changes in peripheral nerve function. Height and circulating inflammatory markers may influence age-related decline in vibrotactile sensitivity through their negative impacts on peripheral nerve function. Vibrotactile sensitivity is directly related to physical performance as demonstrated in an analysis from the InChianti Study, where we found that in the elderly, poor lower limb vibrotactile sensitivity is independently associated with slower self-selected normal gait speed. Thus both sensory and motor components of the peripheral nervous system seem associated with a decline in mobility which subsequently contributes to loss of leg strength and corresponding muscle changes that are major components of the impact of sarcopenia. Based on these observations, we have developed a Cumulative Somatosensory Impairment Index that detects relevant group differences in lower limb somatosensory impairment and is an independent predictor of decline in postural control over 3 years. Such an index may prove useful in assessing future physical functioning problems. The impact of sarcopenia on mortality may in part be dependent on homeostatic factors required in the maintenance of neuromuscular function. We have previously observed that basal metabolic rate declines with age at a rate that accelerated at older ages. Participants who died had a higher basal metabolic rates compared to those who survived independent of other well-recognized risk factors for mortality, such as age, body mass index, smoking, white blood cell count, and diabetes. Further, we have observed that increasing glucose intolerance is associated with increasing mortality independent of the development of diabetes. Recently, we have extended this work to study the relationship of glucose intolerance with changes in muscle mass with aging. Associated with the metabolic changes, we have recently shown that weight loss, which is frequently seen prior to death, often begins 9 or more years before death. This effect is likely related to differences in dietary intake, and energy metabolism during these years prior to death. Age related declines in testosterone in men may be a contributor to losses in muscle strength and physical performance. We previously reported that free testosterone in adult men was modestly but directly related to arm and leg strength independent of fat free mass and age, and indirectly related through body mass. We recently evaluated the question focusing on older men from the InCHIANTI study. Based on baseline serum levels of total testosterone, three different groups of older men were created. With increased severity of hypogonadal status, participants were significantly older with substantially similar body mass indexes. Difference were observed between the groups in hemoglobin levels, hand grip strength and a physical performance score with severely hypogonadal men having lower values of hemoglobin, muscle strength and physical performance. No association was found between group and calf muscle mass and 4 meter walking speed. In the multivariate analysis, grip strength and haemoglobin were the variables significantly different between the 3 groups. These studies demonstrate that in both younger and older men, gonadal status is independently associated with some determinants of physical performance. Another area of interest has been the importance of physical activity and exercise on strength and muscle mass. We have observed that being physically active and maintaining higher intensity activity over time is associated with lower mortality in men, but not women. In women, overall activity, including low and moderate levels, are equally important. Thus, different strategies and activities for men and women might be important. In addition, in the elderly, activity restriction can occur because of fear of falling. We observed that such fears adversely affect physical function and autonomy in the In Chianti population. Thus both psychological and physical factors appear to contribute to fear of falling and the associated restrictions in physical activity. Furthermore, differences in physical and psychosocial characteristics exist between older persons who have fear of falling in community environment activities and those who express fear of falling in home environment activities. These differences suggest the importance of exploring the environment where the fear occurs. Activity interventions need to consider such issues in designing appropriate physical activities and exercise interventions. We have been interested in alternative strategies for exercise intervention for those less inclined to directly exercise including electromyostimulation and a pedometer as a motivational tool to increase activity. Work in this project will continue to explore important physiological, social and activity related factors contributing to strength loss and performance declines with aging. The long term goal is to develop strategies that can be used across the adult lifespan to maintain and improve physical performance. These strategies are likely to differ at different ages, and for women and men.